Judge Juan Pablo Gonzalez of the National Audience, which handles terrorism cases, laid the charges as part of a probe into crimes against humanity that he opened in July in response to a complaint filed by several victims' associations.
The investigation centres on cases of murder or kidnapping carried out by the group since October 1st, 2004, when Spain's criminal code was amended to include a chapter on crimes against humanity.
This includes the bombing of a car park at Madrid airport by Eta militants on December 30th, 2006 in which two Ecuadorian men died.
The judge said the investigation has focused on the suspected leaders of Eta during this period since they "had knowledge of the plan of the crimes that were carried out" during this period and had issued instructions.
Among those charged were the suspected former military heads of Eta, Garikoitz Aspiazu Rubina, alias "Txeroki", and Angel Iriondo Yarza, who were arrested in 2008, Aitor Elizaran Aguilar, the suspected head of Eta's political apparatus who was detained in 2009 and Mikel Carrera Sarobe,
arrested in 2010.
The four are being held in jails in France, where they were arrested.
The judge also charged Jose Antonio Urruticoetxea, also known as "Josu Ternera", a veteran leader of Eta between 1977 and 1992, who has been on the run since he escaped arrest in France in 2013.
Eta is accused of killing 829 people in a four-decade campaign for the independence of the Basque region, which straddles the French and Spanish border.
It announced the end of its armed campaign in October 2011, but has refused to hand over its weapons or dissolve the organisation, as demanded by governments in both countries.
Eta began a unilateral disarmament programme in early 2014, in cooperation with the International Verification Commission, an independent group of experts from various countries that has not been officially recognised by the Spanish government.
The group is considered to be a terrorist organisation by the European Union.